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Stanley N. Cohen Papers

 Collection
Identifier: MS C 623

Abstract

Correspondence, email and electronic records, laboratory notebooks and workpapers, grant files, reports and journal articles, notes, lectures, awards, honors, and memorabilia document the academic and professional career of Stanford University geneticist Stanley N. Cohen. The collection comprehensively covers the many facets of Cohen's career from his early work in computational medical diagnosis, to the discovery of recombinant DNA technology, to contemporary research on degenerative neurological diseases.

Dates

  • 1948-2016

Extent

120 Linear Feet (99 boxes + 36.6 GB electronic records)

Creator

Physical Location

Materials stored onsite. History of Medicine Division. National Library of Medicine

Language of Materials

Collection materials primarily in English

Access Restrictions

No restrictions on access.

Copyright and Re-use Information

Donor's copyrights were transferred to the public domain.

Privacy Information

Archives and manuscript collections may contain materials with sensitive or confidential information that is protected under federal or state right to privacy laws and regulations. Researchers are advised that the disclosure of certain information pertaining to identifiable living individuals represented in any collection without the consent of those individuals may have legal ramifications for which the National Library of Medicine assumes no responsibility.

Biographical Note

Born in Perth Amboy, New Jersey February 17, 1935, Stanley Norman Cohen is Kwoh-Ting Li professor of genetics at Stanford University School of Medicine. Cohen and UC San Francisco scientist Herbert Boyer were the first scientists to transplant genes from one living organism to another and is often considered the birth of genetic engineering and DNA therapies. In addition to the medical advances produced by their work, the financial impact of the patents for the Boyer-Cohen processes to both Stanford and UCSF marked a shift in the way universities recognized the commercial value of their scientists and helped launch the nascent biotechnology industry. Cohen's DNA cloning research was the result of his interest in basic scientific inquiry into fundamental natural phenomena, not to create new tools for diagnosing human disease. This ethos and commitment to basic scientific research is a defining principle of Cohen's work.

Cohen was raised and educated in the Garden State. His broad range of intellectual curiosity, though not confined to academia, led to distinctive scholarly achievements at Perth Amboy High School and Rutgers University. In additional to his scientific skills, young Cohen was a successful debater, banjo and ukulele musician, and published pop music composer. After graduating from Rutgers Cohen shifted his scientific ambitions from physics to medicine and continued his studies at the University of Pennsylvania School of Medicine, where he graduated with a medical degree in 1960.

For the next seven years, Dr. Cohen held internships and fellowships at Mt. Sinai Hospital in New York City, University Hospital in Ann Arbor, Michigan, and Duke University Hospital in Durham, North Carolina, among other institutions. While at the National Institute for Arthritis and Metabolic Diseases he refocused his efforts toward a combination of basic research with clinical practice. As a post-doctoral researcher at the Albert Einstein College of Medicine in 1967 he taught while also studying the mechanisms which control gene expression.

Upon accepting a position with Stanford University in 1968, Dr. Cohen began experimenting with plasmids to understand the mechanisms that underlie antibiotic resistance. Plasmids are genetic elements within bacteria. They independently reproduce within bacteria molecules, generating drug resistance genes. As such, plasmids are an obvious starting point for studying how and why bacteria develop resistance to antibiotics. To do this work it was necessary to develop a way to pull plasmids apart, glue segments of them back together again, then propagate and clone new combinations of plasmid genes in living cells.

In collaboration with Norman Davidson and Phillip Sharp at Caltech, Dr. Cohen's lab initiated a plasmid study using electron microscopy. These investigations proved a link between bacterial DNA carried in plasmids and the formation of resistance-plasmid DNA.

A necessary next step in studying the molecular biology of plasmids was the reintroduction of plasmid DNA molecules into bacteria. By isolating drug resistant plasmid DNA and placing it into bacteria, the reaction could be studied. Specifically, one could learn whether new non-drug-resistant plasmids were produced. If such reproduction occurred, plasmid DNA could be a starting point for instigating the generation of large quantities of DNA in bacteria. Initially these investigations were hampered by the method of isolation and reintroduction.

Mechanical shearing broke apart plasmid molecules, producing fragmented plasmid DNA. Fragmented resistance plasmid DNA was put into bacteria and the reaction studied. Shearing proved too imprecise a method, fragments didn't cleanly interact, and the resulting insights were minimal.

A more precise method for cutting plasmid DNA molecules was introduced in 1970 which used enzymes. An endonuclease, or enzyme, is a protein that functions as a catalyst in regulating chemical reactions in an organism. It was found that certain endonucleases naturally cut up foreign DNA which may be present in bacteria. Called restriction endonucleases, endonucleases cut DNA in precise, site-specific locations, in a way that left "sticky" ends, which were ideally suited to bond with other DNA.

If a restriction endonuclease could be adapted to cut DNA within a plasmid and the resulting plasmid were reintroduced into bacteria and it reproduced, DNA, or genetic, cloning would be achieved; the process of inducing the production of genetically identical substances.

In 1972 Dr. Cohen began a collaboration with Dr. Herbert Boyer, of the University of California, San Francisco. Dr. Boyer had demonstrated the viability of a restriction endonuclease in E. Coli, known as EcoRI. Dr. Cohen used it to clone antibiotic resistance genes in plasmids. This innovative technique, known as recombinant DNA technology, was patented by Drs. Cohen and Boyer in 1980, one of the first biotechnology patents. Before its expiration in 1997, the patent issued 461 licenses.

Shortly after his initial success, Dr. Cohen combined staphylococcus aureus DNA and E. coli DNA in an experiment proving the hypothesis that interspecies cloning was possible. This demonstration raised fears about biohazard safety and ethical concerns over cloning technology in the scientific community. In 1975 the influential Asilomar Conference on Recombinant DNA conference organized by Paul Berg was held to discuss the potential biohazards and regulation of biotechnology. A group of about 140 professionals (primarily biologists, but also including lawyers and physicians) participated in the conference to draw up voluntary guidelines to ensure the safety of recombinant DNA technology. The U.S. government, in an attempt to regulate and develop formal policies for how to conduct DNA research, created the Recombinant DNA Advisory Committee which published the Recombinant DNA Research Guidelines in 1976. Cohen argued throughout these debates that recommended containment levels for certain types of research should be lowered on the grounds that there is little risk involved. In the ensuing decades recombinant DNA technology has enhanced substances in a variety of fields, including biotechnology, medicine, medical research, food production, agriculture, and industry, and has spawned the field of genomics. This field of research intentionally also served to bring scientific research more into the public domain.

Dr. Cohen's lab has long been interested in the evolution and dissemination of antibiotic resistance, and continues to pursue these interests by investigating the biology underlying the ability of bacteria to adapt non-mutationally to antibiotic exposure and other environmental stresses via the study of plasmid inheritance, cell growth, mobile genetic elements, cancers, viruses, toxins, and drug therapy. As of 2017 the lab's research interests include how expansion of gene regions containing nucleotide repeats (NRs) has a causal role in a variety of inherited degenerative neurological diseases, including Huntington's Disease, certain spinocerebellar ataxias and muscular dystrophies, and some types of amyotrophic lateral sclerosis and frontotemporal dementia. This involves the study of mechanisms that selectively enable transcription through expanded NR regions in human genes, actions of abnormal mRNAs and proteins generated by such repeats, and efforts at treating those diseases by targeting expression of the abnormal genes.

Lastly, Dr. Cohen was a primary figure in the establishment of collaborative research with the Institute of Molecular Biology in Taipei and in helping to establish a biotechnology industry in Taiwan. For his significant scientific contributions Cohen has received the Albert and Mary Lasker Award, the Wolf Foundation Prize, the Presidential Medal of Science, and election to the Inventors' Hall of Fame, among many other honors.

Collection Summary

Correspondence, email and electronic records, laboratory notebooks and workpapers, grant files, reports and journal articles, notes, lectures, awards, honors, and memorabilia document the academic and professional career of Stanford University School of Medicine geneticist Stanley N. Cohen. The collection comprehensively covers the many facets of Cohen's career from his early work in artificial intelligence medical diagnosis, his discovery of recombinant DNA technology, the development of laboratory safety standards, the promotion of public knowledge about science, and the ongoing focus of his lab in the areas of plasmid inheritance, cell growth, mobile genetic elements.

Series 1, Personal and Biographical (1948-2015), illustrates Dr. Cohen's academic achievements as well as his avocations. This includes certificates, diplomas, and yearbooks documenting his professional advancement, along with ephemera relating to his musical and songwriting work and the Society for Medical Friends of Wine. Several folders of clippings (1970-2013) contain articles about Dr. Cohen's career, DNA technology in general, as well as significant items of correspondence. Photographs, correspondence, and website archives for the several Cohen Birthday Symposia celebrate the successes of his lab, colleagues, and staff as well as serve as forums for invitees to discuss and present new areas of research.

Series 2, Correspondence (1968-2015) is divided into three subseries: chronological files of daily office activity (1977-1996), corporate correspondence (1970-2015), and files by personal name (1968-2011). The series also contains 65 computer discs of correspondence dating from 1979-1986 and email archives dated 1999-2016.

Series 3, Recombinant DNA (1977-1992) contains a few articles about recombinant DNA along with documentation of the process of the Cogene working group's formulation of guidelines for the safe and ethical use of cloning technology.

Series 4, Lab Administration (1972-1999) briefly chronicles some of the business and management activities of Cohen's lab. Developing protocols and procedures for the safe handling of biohazardous materials was also a significant outcome of the recombinant DNA work and the Cohen lab administration manual became a model for working safely in the lab and safely conduct experiments. Cohen's work during a sabbatical year to Taiwan University was to establishment a joint biotechnology research venture between Stanford and National Taiwan University (1991-1999) is documented through correspondence and project application files of the Chinese students working in the program.

Series 5, Lab Notebooks and Workpapers (1963-2010) contains laboratory notebooks, notes, and correspondence produced by researchers in Dr. Cohen's Stanford lab. The lab notebooks contain experiment data; Workpapers is a descriptive term Cohen uses to describe the manuscript drafts and editorial and collaborator correspondence and notes that along with lab data form the final research products. The nine notebooks produced by Dr. Cohen in this series (1963-1967) are representative examples of his postdoctoral research predate his work at Stanford; the lab notebooks for his seminal plasmid DNA work are located in the Smithsonian Museum of American History as are the physical components of the lab and equipment where the work was conducted.

Series 6, Publication Activity (1959-2016) represents scientific articles authored and co-authored by Dr. Cohen. Numbered articles total 364 but are complete only through the first 200. Those numbered beyond 200 exist variously as drafts, reprints, and correspondence. Many of the later articles exist in this collection only in digital form. This section also contains articles by Dr. Cohen (1959-2001) not represented in the numbered bibliography, and drafts and correspondence for seemingly unpublished articles (1975-1991).

Series 7, Lectures (1977-2016) consists of correspondence, brochures, announcements, notes, and speeches given by Dr. Cohen at various lectureships, conferences, symposia, and on special occasions. One section is devoted to a particular speech Dr. Cohen developed in response to the general public's reaction to the implications of cloning technology. "Fear of Knowledge" addresses the general phenomenon of fearing knowledge and relates it directly to responses to his work with recombinant DNA and stresses the need to promulgate scientific knowledge as beneficial.

Series 8, Stanford School of Medicine Genetics Department (1976-2008) contains lecture outlines, lectures, reading lists, readings, examination questions, and syllabi for courses taught by Dr. Cohen at Stanford: Clinical Pharmacology 202, Genetics 201, 202, 208, 209, Pharmacology, other miscellaneous course outlines including graduate medical education material. Dr. Cohen taught medical courses prior to being appointed professor of genetics in 1977 and was department chair.

Series 9, Contracts and Grants (1967-2010) contain guidelines and reports from various research grants Dr. Cohen's laboratory mostly involving genetic research, but also highlights the other clinical diagnostic fields Cohen worked in especially in the artificial intelligence and computational diagnostic arenas. Among the subjects studied were the evolution of plasmids through the American Cancer Society (1979-1993); ovarian and prostate cancer with the California Cancer Research Program (1998-2003); toxins in mammals and viral pathogens with the Defense Advance Research Projects Agency (DARPA); and genetics, propagation and inheritance of plasmids, genomic DNA cloning and analysis, computer-based online drug therapy monitoring/Mediphor (1970s-1986), computer intervention in clinical drug therapy/Minerva (1977-1983), computational medical diagnosis/MYCIN research with Edward Shortliffe, and tumor suppression gene with NIH (1971-2002). The series also contains an alphabetical list of funding sources.

Series 10, Material Transfer Agreements (1968-2006) contains records of agreements and transfers made of plasmid DNA strains requested for cloning, documentation of the development of terminology and procedures, and requests for transfers of random homozygous knockout, a mutated gene made to replace a normal genome to study its functions in a live organism.

Series 11, Cohen/Boyer Patent (1972-2003) contains legal and administrative documents for preparing recombinant DNA patent applications and the subsequent management of royalties and technology usage rights. The materials include legal discussions and debates about the Cohen/Boyer original patent application, technology transfer, royalties, and material usage agreements. It also includes the original patent certificate.

Series 12, Travel, Meetings, and Seminars (1976-2016), contains brochures, proceedings, agendas, and notes from professional scientific meetings, conferences and symposia Dr. Cohen attended. Among the most frequently attended were meetings with the National Academy of Sciences/PNAS, Gordon research conference, American Society for Microbiology, Institute of Molecular Biology (Taiwan), Federation of American Societies for Experimental Biology, Defense Advanced Research Projects Agency (DARPA), and Singapore Economic Development Board (EDB).

Series 13, Memberships and Awards (1955-2016), holds certificates, plaques, and artifacts presented to Dr. Cohen. Notable among these are honorary doctorates from Rutgers University and the University of Pennsylvania, the Lasker Award, the Shaw Prize, the Wolf Foundation Prize, the National Medal of Science, the National Medal of Technology, and certificate of induction into the Inventors' Hall of Fame. Certificates and other documentation represent Dr. Cohen's membership in various medical societies and academies.

Abstract

Correspondence, email and electronic records, laboratory notebooks and workpapers, grant files, reports and journal articles, notes, lectures, awards, honors, and memorabilia document the academic and professional career of Stanford University geneticist Stanley N. Cohen. The collection comprehensively covers the many facets of Cohen's career from his early work in computational medical diagnosis, to the discovery of recombinant DNA technology, to contemporary research on degenerative neurological diseases.

Physical Location

Materials stored onsite. History of Medicine Division. National Library of Medicine

Provenance

Gift, Stanley Cohen, 2016 Aug. 23, Accession #2016-025, 2016-033a, 2017-022.

General

Processed by
Jim Labosier
Processing Completed
March 2018
Encoded by
Jim Labosier
Title
Finding Aid to the Stanley N. Cohen Papers, 1948-2016
Status
Unverified Partial Draft
Author
Jim Labosier
Date
March 2018
Language of description
English
Script of description
Latn
Language of description note
Finding aid is written in English English
Edition statement
1.0

Collecting Area Details

Part of the Archives and Modern Manuscripts Collection Collecting Area

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